Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions

In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DATIREScre mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome

The repeatability and reproducibility of four techniques for measuring horizontal heterophoria: Implications for clinical practice

PURPOSE: Convergence insufficiency, the most common binocular vision anomaly, is characterised by a receded near point of convergence and an exophoria which is at least 4 prism dioptres (Δ) larger at near than at distance. However, the repeatability of standard heterophoria measures are poorly understood. This study assessed the ability of four common heterophoria tests to detect differences of 4Δ by evaluating the inter- and intra-examiner variability of the selected techniques. METHODS: Distance and near horizontal heterophorias of 20 visually-normal adults were measured with the alternating prism cover test, von Graefe prism dissociation, Howell Card and Maddox Rod by two examiners at two separate visits using standardised instructions and techniques. We investigated inter- and intra-examiner variability using repeatability and reproducibility indices, as well as Bland-Altman analysis with acceptable limits of agreement defined as ±2Δ. RESULTS: The Howell card test had the lowest intra-examiner variability at both distance and near, as well as the best 95% limits of agreement (±1.6Δ for distance and ±3.7Δ for near). Inter-examiner reproducibility results were similar, although at near the alternating prism cover test had better repeatability (1.1Δ, 95% confidence intervals −1.1Δ to 4.0Δ) than the Howell card (1.4Δ, 95% confidence intervals −1.9Δ to 5.9Δ). CONCLUSION: The low repeatability of many standard clinical heterophoria tests limits the ability to reliably detect a 4Δ difference. The Howell Card provided the most repeatable and reproducible results indicating that this technique should be used to detect small changes in heterophoria magnitude and direction

Calcareous phytoplankton response to the half century of interannual climatic variability in Santa Barbara Basin (California)

A high-resolution study of calcareous phytoplankton in a box core from the Santa Barbara Basin (SBB) reveals floral assemblage fluctuations which can be related to climatic and paleoceanographic changes during the last half century (1940-1996). In particular, Gephyrocapsa oceanica production increased during El Niño periods, in response to high temperatures, silica depletion, and increased iron availability. Conversely, Helicosphaera carteri flux increases in conjunction with lower surface temperatures associated with La Niña episodes. Increasing abundances of Florisphaera profunda and Umbilicosphaera sibogae after 1970 reflect a warming trend and increased stratification within the basin associated with the warm phase of the Pacific Decadal Oscillation (PDO). Conversely, increased abundances of Coccolithus pelagicus and Calcidiscus leptoporus before 1970 mark the cold phase of PDO. These coccolithophore production rate data are consistent with instrumental records of surface and thermocline temperatures monitored since 1950. This is the first study to document the response of calcareous phytoplankton to surface water warming occurring in SBB since 197

A horizon scan of issues affecting UK forest management within 50 years

Forests are in the spotlight: they are expected to play a pivotal role in our response to society’s greatest challenges, such as the climate and biodiversity crises. Yet, the forests themselves, and the sector that manages them, face a range of interrelated threats and opportunities. Many of these are well understood, even if the solutions remain elusive. However, there are also emerging trends that are currently less widely appreciated. We report here the results of a horizon scan to identify developing issues likely to affect UK forest management within the next 50 years. These are issues that are presently under-recognized but have potential for significant impact across the sector and beyond. As the forest management sector naturally operates over long timescales, the importance of using good foresight is self-evident. We followed a tried-and-tested horizon scanning methodology involving a diverse Expert Panel to collate and prioritize a longlist of 180 issues. The top 15 issues identified are presented in the Graphical Abstract. The issues represent a diverse range of themes, within a spectrum of influences from environmental shocks and perturbations to changing political and socio-economic drivers, with complex emerging interactions between them. The most highly ranked issue was ‘Catastrophic forest ecosystem collapse’, reflecting agreement that not only is such collapse a likely prospect but it would also have huge implications across the sector and wider society. These and many of the other issues are large scale, with far-reaching implications. We must be careful to avoid inaction through being overwhelmed, or indeed to merely focus on ‘easy wins’ without considering broader ramifications. Our responses to each of the challenges and opportunities highlighted must be synergistic and coherent, involving landscape-scale planning. A more adaptive approach to forest management will be essential, encouraging continual innovation and learning. The 15 horizon scan issues presented here are a starting point on which to build further research, prompt debate and action, and develop evidence-based policy and practice. We hope that this stimulates greater recognition of how our forests and sector may need to change to be fit for the future. In some cases, these changes will need to be fundamental and momentous

Longitudinal associations between circulating interleukin-6 and C-reactive protein in childhood, and eating disorders and disordered eating in adolescence

Objective: Few studies have explored the association between inflammation and eating disorders and none used a longitudinal design. We investigated the association between serum-levels of interleukin 6 (IL-6) and C-reactive protein (CRP) measured in childhood and eating disorders and related behaviours and cognitions in adolescence in a large general population sample. Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Our exposures were thirds of IL6 and CRP derived from serum measurements taken at age nine years, and outcomes were eating disorder diagnoses and self-reported disordered eating behaviours at ages 14, 16, and 18 years. We used univariable and multivariable multilevel logistic regression models adjusting for a number of potential confounders, including sex, fat mass, and pre-existing mental health difficulties. Results: Our sample included 3480 children. Those in the top third of CRP had lower odds of binge eating (odds ratio(OR):0.62, 95% confidence interval (CI):0.39,1.00,p “equals” 0.05) and fasting (OR:0.63, 95% CI:0.38,1.07,p “equals” 0.09) after adjustment for confounders. We also observed weak associations of comparable magnitude for purging, anorexia nervosa, and bulimia nervosa. We did not find any associations between levels of IL6 and any of the outcomes under study. Conclusions: There was little evidence of an association between CRP and IL-6 and adolescent eating disorder outcomes. The inverse association observed between CRP and binge eating was unexpected, so caution is needed when interpreting it. One possible explanation is that higher CRP levels could have a protective role for disordered eating by affecting appetitive traits

Integrated Analysis of Human Milk Microbiota With Oligosaccharides and Fatty Acids in the CHILD Cohort

Background: Human milk contains many bioactive components that are typically studied in isolation, including bacteria. We performed an integrated analysis of human milk oligosaccharides and fatty acids to explore their associations with milk microbiota.Methods: We studied a sub-sample of 393 mothers in the CHILD birth cohort. Milk was collected at 3–4 months postpartum. Microbiota was analyzed by 16S rRNA gene V4 sequencing. Oligosaccharides and fatty acids were analyzed by rapid high-throughput high performance and gas liquid chromatography, respectively. Dimension reduction was performed with principal component analysis for oligosaccharides and fatty acids. Center log-ratio transformation was applied to all three components. Associations between components were assessed using Spearman rank correlation, network visualization, multivariable linear regression, redundancy analysis, and structural equation modeling. P-values were adjusted for multiple comparisons. Key covariates were considered, including fucosyltransferase-2 (FUT2) secretor status of mother and infant, method of feeding (direct breastfeeding or pumped breast milk), and maternal fish oil supplement use.Results: Overall, correlations were strongest between milk components of the same type. For example, FUT2-dependent HMOs were positively correlated with each other, and Staphylococcus was negatively correlated with other core taxa. Some associations were also observed between components of different types. Using redundancy analysis and structural equation modeling, the overall milk fatty acid profile was significantly associated with milk microbiota composition. In addition, some individual fatty acids [22:6n3 (docosahexaenoic acid), 22:5n3, 20:5n3, 17:0, 18:0] and oligosaccharides (fucosyl-lacto-N-hexaose, lacto-N-hexaose, lacto-N-fucopentaose I) were associated with microbiota α diversity, while others (C18:0, 3′-sialyllactose, disialyl-lacto-N-tetraose) were associated with overall microbiota composition. Only a few significant associations between individual HMOs and microbiota were observed; notably, among mothers using breast pumps, Bifidobacterium prevalence was associated with lower abundances of disialyl-lacto-N-hexaose. Additionally, among non-secretor mothers, Staphylococcus was positively correlated with sialylated HMOs.Conclusion: Using multiple approaches to integrate and analyse milk microbiota, oligosaccharides, and fatty acids, we observed several associations between different milk components and microbiota, some of which were modified by secretor status and/or breastfeeding practices. Additional research is needed to further validate and mechanistically characterize these associations and determine their relevance to infant gut and respiratory microbiota development and health

A horizon scan of issues affecting UK forest management within 50 years

Forests are in the spotlight: they are expected to play a pivotal role in our response to society’s greatest challenges, such as the climate and biodiversity crises. Yet, the forests themselves, and the sector that manages them, face a range of interrelated threats and opportunities. Many of these are well understood, even if the solutions remain elusive. However, there are also emerging trends that are currently less widely appreciated. We report here the results of a horizon scan to identify developing issues likely to affect UK forest management within the next 50 years. These are issues that are presently under-recognized but have potential for significant impact across the sector and beyond. As the forest management sector naturally operates over long timescales, the importance of using good foresight is self-evident. We followed a tried-and-tested horizon scanning methodology involving a diverse Expert Panel to collate and prioritize a longlist of 180 issues. The top 15 issues identified are presented in the Graphical Abstract. The issues represent a diverse range of themes, within a spectrum of influences from environmental shocks and perturbations to changing political and socio-economic drivers, with complex emerging interactions between them. The most highly ranked issue was ‘Catastrophic forest ecosystem collapse’, reflecting agreement that not only is such collapse a likely prospect but it would also have huge implications across the sector and wider society. These and many of the other issues are large scale, with far-reaching implications. We must be careful to avoid inaction through being overwhelmed, or indeed to merely focus on ‘easy wins’ without considering broader ramifications. Our responses to each of the challenges and opportunities highlighted must be synergistic and coherent, involving landscape-scale planning. A more adaptive approach to forest management will be essential, encouraging continual innovation and learning. The 15 horizon scan issues presented here are a starting point on which to build further research, prompt debate and action, and develop evidence-based policy and practice. We hope that this stimulates greater recognition of how our forests and sector may need to change to be fit for the future. In some cases, these changes will need to be fundamental and momentous

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

A horizon scan of issues affecting UK forest management within 50 years

Forests are in the spotlight: they are expected to play a pivotal role in our response to society’s greatest challenges, such as the climate and biodiversity crises. Yet, the forests themselves, and the sector that manages them, face a range of interrelated threats and opportunities. Many of these are well understood, even if the solutions remain elusive. However, there are also emerging trends that are currently less widely appreciated. We report here the results of a horizon scan to identify developing issues likely to affect UK forest management within the next 50 years. These are issues that are presently under-recognized but have potential for significant impact across the sector and beyond. As the forest management sector naturally operates over long timescales, the importance of using good foresight is self-evident. We followed a tried-and-tested horizon scanning methodology involving a diverse Expert Panel to collate and prioritize a longlist of 180 issues. The top 15 issues identified are presented in the Graphical Abstract. The issues represent a diverse range of themes, within a spectrum of influences from environmental shocks and perturbations to changing political and socio-economic drivers, with complex emerging interactions between them. The most highly ranked issue was ‘Catastrophic forest ecosystem collapse’, reflecting agreement that not only is such collapse a likely prospect but it would also have huge implications across the sector and wider society. These and many of the other issues are large scale, with far-reaching implications. We must be careful to avoid inaction through being overwhelmed, or indeed to merely focus on ‘easy wins’ without considering broader ramifications. Our responses to each of the challenges and opportunities highlighted must be synergistic and coherent, involving landscape-scale planning. A more adaptive approach to forest management will be essential, encouraging continual innovation and learning. The 15 horizon scan issues presented here are a starting point on which to build further research, prompt debate and action, and develop evidence-based policy and practice. We hope that this stimulates greater recognition of how our forests and sector may need to change to be fit for the future. In some cases, these changes will need to be fundamental and momentous